Analyzer, and method of detection liquid level in an analyzer

ABSTRACT

Disclosed is an analyzer comprising: a container holder configured to hold a container containing a liquid; an aspirating tube configured to aspirate the liquid from the container held by the container holder; a drive part configured to transfer the aspirating tube; a detector configured to output a signal based on a physical characteristic between the aspirating tube and a liquid surface of the liquid in the container; and a memory configured to store, as a reference signal, the signal output from the detector when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder; and a controller configured to detect the liquid level position of the liquid in the container, based on the reference signal and a real signal that the detector outputs, when the aspirating tube is transferred for an aspiration operation of the liquid.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from prior Japanese Patent Application No. 2014-060393, filed on Mar. 24, 2014, entitled “ANALYZER, AND METHOD OF DETECTION LIQUID LEVEL IN AN ANALYZER”, the entire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to an analyzer and a method of detecting liquid level in an analyzer. More specifically, the present invention relates to an analyzer and method of detecting liquid level in an analyzer capable of accurately detecting the level of a liquid such as a sample and reagent aspirated from a container by an aspirating tube.

BACKGROUND

Conventional sample analyzers are known to dispense a sample such as blood or urine from a sample container to a reaction vessel where the sample is mixed with a reagent corresponding to the measurement criteria, and then perform various types of measurements and analyses. The liquids, such as sample and reagent, used in this sample analyzer are stored in predetermined containers and aspirated by an aspirating tube which is inserted into the container. There is known art for preventing contamination and minimizing the amount of insertion of the nozzle in the liquid by detecting the liquid level in the container (refer to Japanese Laid-Open Patent Application No. H11-271319).

The art disclosed in Japanese Laid-Open Patent Application No. H11-271319 detects changes in the electrostatic capacity between the liquid and the aspirating tube to detect the liquid level within the container. The static electricity is eliminated to prevent inaccurate detection of the liquid level due the influence of the static electricity charging the container.

Static electricity is just one of several factors obstructing liquid level detection. For example, when detecting the liquid level based on changes in electrostatic capacity as in the art disclosed in Japanese Laid-Open Patent Application No. H11-271319, there may be conductors such as metal panels and screws around the container and these conductors can act as electrodes to greatly change the electrostatic capacity. Therefore, when there is a change in electrostatic capacity while detecting the liquid level, it becomes difficult to recognize the change in electrostatic capacity when the aspirating tube approaches a nearby conductor and the liquid level cannot be accurately detected. There also is concern that liquid level detection also will become inaccurate due to changes in the detected electrostatic capacity caused by loosening of a metal screw around the container and by a replaced metal part. There is further concern that liquid level detection will be inaccurate due to changes in detected voltage caused by differences in the shapes of containers holding the liquid when liquid level detection is performed by a voltage sensor. Hence, the environment surrounding the liquid level sensor greatly affects the detection signal of the liquid level sensor.

SUMMARY OF INVENTION

The scope of the present invention is defined solely by the appended claims, and is not affected to any degree by the statements within this summary.

A first aspect of the present invention is An analyzer comprising: a container holder configured to hold a container containing a liquid; an aspirating tube configured to aspirate the liquid from the container held by the container holder; a drive part configured to transfer the aspirating tube; a detector configured to output a signal based on a physical characteristic between the aspirating tube and a liquid surface in the container; and a memory configured to store, as a reference signal, the signal output from the detector when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder; and a controller configured to detect a liquid level position in the container, based on the reference signal and a real signal output by the detector when the aspirating tube is transferred for an aspiration operation of the liquid.

A second aspect of the present invention is an analyzer comprising: a container holder configured to hold a container containing a liquid; an aspirating tube configured to aspirate the liquid from the container held by the container holder; a drive part configured to transfer the aspirating tube; a controller configured to control the drive part; a detector configured to output a signal based on a physical characteristic between the aspirating tube and a liquid surface in the container; and a memory configured to store the signal output by the detector; wherein the controller is configured to; store as a reference signal in the memory, the signal output by the detector when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder; and detect the liquid level position in the container, based on the reference signal and a real signal output by the detector when the aspirating tube is transferred for an aspiration operation of the liquid.

A third aspect of the present invention is a method of detecting a liquid level in an analyzer comprising: a step of transferring an aspirating tube to aspirate a liquid from a container held in a container holder; a step of outputting, as a real signal, a signal based on a physical characteristic between the aspirating tube and a liquid surface in the container, when the aspirating tube is being transferred for an aspiration operation of the liquid; and a step of detecting the liquid level position in the container based on the real signal and a reference signal that is based on a physical characteristic between the aspirating tube and the liquid surface in the container when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing the general structure of an immunoanalyzer 1 as an embodiment of the sample analyzer;

FIG. 2 is a plan view of the immunoanalyzer of FIG. 1;

FIG. 3 is a perspective view of a reagent installation unit;

FIG. 4 is a side view briefly showing the structure of a reagent dispensing unit;

FIG. 5 is a block diagram showing the structure of a liquid level detector;

FIG. 6 is a block diagram showing the structure of a capacitance detector;

FIG. 7 illustrates the correspondence between the position of the aspirating tube in the vertical direction and the background signal;

FIG. 8 illustrates the correspondence between the position of the aspirating tube in the vertical direction, the liquid level detection signal, and the differential signal;

FIG. 9 is a flow chart showing the procedure of obtaining the background signal;

FIG. 10 is a flow chart showing the control sequence of the reagent aspirating operation by the aspirating tube;

FIG. 11 is a flow chart showing the control sequence of the reagent aspirating operation by the aspirating tube;

FIG. 12 is a flow chart showing the control sequence of the aspirating tube washing process; and

FIG. 13 is a cross sectional view of the aspirating tube washing unit.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The preferred embodiments will be described hereinafter with reference to the drawings.

[General Structure of Immunoanalyzer 1]

The immunoanalyzer 1 examines various items such as hepatitis type-B, hepatitis type-C, tumor marker, and thyroid hormone contained in a plasma sample (hereinafter referred to simply as “sample”) by utilizing an antigen/antibody reaction. The immunoanalyzer 1 has a measuring section 2, sample transporting section 3, and a control device 4. The measuring section 2 is connected to the sample transporting section 3 and the control device 4 with communication enabled. The sample transporting section 3 is configured to transport a rack holding a plurality of test tubes containing sample collected from a subject. The control device 4 has a main body 400 and a display/input section 410. The display/input section 410 has a touch panel, and incorporates a display section and input section.

As shown in FIG. 2, the measuring section 2 includes a sample dispenser 5, R1 reagent dispenser 6, R2 reagent dispenser 7, R3 reagent dispenser 8, reactor 9, cuvette supplier 10, Primary BF separator 11, secondary BF separator 12, pipette tip supplier 13, measuring unit 14, R4/R5 reagent supplier 15, reagent installation section 16, disposal unit 17, and measurement controller 200 (refer to FIG. 1).

The sample transporting section 3 is configured to transport a rack holding a plurality of test tubes containing unprocessed sample.

In the immunoanalyzer 1, the sample to be measured is mixed with a buffer solution R1 reagent, and an R2 reagent which contains magnetic particles carrying a capture antibody for binding to the antigen in the sample is added to the liquid mixture. The components in the sample that are not bound to the capture antibody are eliminated when magnetic particles carrying the capture antibody bound to the antigen are attracted to a magnet (not shown in the drawing) of the primary BF (bound free) separator 11. After an R3 reagent containing a labeled antibody has been added, the magnetic particles carrying the capture antibody bound to the antigen and the labeled antibody are attracted to a magnet of the secondary BF separator 12 (not shown in the drawing) to eliminate the R3 reagent that contains the unreacted labeled antibody. After adding an R5 reagent containing a luminescent substrate, which luminesces via reaction between the labeled antibody and the R4 reagent which is a dispersion liquid, the amount of light produced by the reaction between the labeled antibody and the luminescent substrate is measured. The antigen contained in the sample bound to the labeled antibody can be quantified through this process.

The cuvette supplier 10 is configured to accommodate a plurality of cuvettes, and sequentially supplies the cuvettes one by one to the discharge position 1 b.

An aspirating tube 6 a for aspirating and discharging R1 reagent is attached to the R1 reagent dispenser 6, as shown in the drawing. A pipette is used as the aspirating tube 6 a in the present embodiment. The R1 reagent dispenser 6 aspirates the R1 reagent from the reagent container installed in the reagent installation section 16, and discharges the aspirated R1 reagent to a cuvette placed at the discharge position 1 b using the aspirating tube 6 a.

The pipette tip supplier 13 moves a plurality of loaded pipette tips (not shown in the drawing) one by one to the tip installation position (not shown in the drawing). Thereafter, a pipette tip is mounted on the pipette end of the sample dispenser 5 at the tip installation position.

The sample dispenser 5 aspirates the sample in the test tube moved to the sample aspirating position 1 a by the sample transporting section 3 using the installed pipette tip. This aspiration is accomplished through a hole 31 a formed in a cover 31 that covers the transport path of the sample transporting section 3. The sample dispenser 5 discharges the aspirated sample into a cuvette at the discharge position 1 b. The R1 reagent was previously dispensed to the cuvette by the R1 reagent dispenser 6. Thereafter, the cuvette is moved to the reactor 9 by a catcher (not shown in the drawing) of the R1 reagent dispenser 6.

As shown in the drawing, an aspirating tube 7 a for aspirating and discharging R2 reagent is attached to the R2 reagent dispenser 7. A pipette is used as the aspirating tube 7 a in the present embodiment. The R2 reagent dispenser 7 aspirates the R2 reagent from the reagent container installed in the reagent installation section 16, and discharges the aspirated R2 reagent to a cuvette containing the R1 reagent and the sample.

The reactor 9 has an annular shape so as to circumscribe the reagent installation section 16, which is circular, as shown in the drawing. The reactor 9 has a plurality of cuvette holders 9 a arranged at predetermined spacing along the exterior. Cuvettes set in the cuvette holders 9 a are heated to approximately 42° C. Hence, the heating promotes reaction of the various reagents and the sample in the cuvette. The reactor 9 is configured to be horizontally rotatable in a clockwise direction, and moves the cuvette set in the cuvette holder 9 a to each processing position where various processes, such as dispensing reagent, are performed.

The cuvette containing the sample and R1 and R2 reagents is moved by a catcher (not shown in the drawing) from the reactor 9 to the primary BF separator 11. Primary BF separation is performed by the primary BF separator 11. The components in the sample that are not bound to the capture antibody of the R2 reagent are thus removed from the sample within the cuvette. Having completed primary BF separation, the cuvette is returned to the reactor 9 by the catcher (not shown).

An aspirating tube 8 a for aspirating and discharging R3 reagent is attached to the R3 reagent dispenser 8, as shown in the drawing. A pipette is used as the aspirating tube 8 a in the present embodiment. The R3 reagent dispenser 8 uses the aspirating tube 8 a to aspirate the R3 reagent set at the reagent installation section 16. The R3 reagent dispenser 8 also uses the aspirating tube 8 a to discharge the aspirated R3 reagent into the cuvette which was moved from the primary BF separator 11 to the reactor 9.

After the elimination process by the primary BF separator 11, the cuvette containing the R3 reagent and the sample already processed by the primary BF separator 11 is moved from the reactor 9 to the secondary BF separation section 12 by a catcher (not shown in the drawing). Secondary BF separation is performed in the secondary BF separator 12. The R3 reagent including the unreacted labeled antibody is thereby eliminated. Having completed secondary BF separation, the cuvette is returned to the reactor 9 by the catcher (not shown).

The R4/R5 reagent supplier 15 sequentially dispenses R4 and R5 reagents to the cuvette containing the sample after the elimination process performed by the secondary BF separator 12 via a catcher not shown in the drawing.

The reagent installation section 16 holds a plurality of reagent containers which accommodate R1 reagent, R2 reagent, and R3 reagent, respectively, for each measurement item. The reagent installation section 16 also holds a container of BSA duffer as a sample buffering solution, which is used to dilute the sample when dilute sample measurements are performed.

The measuring unit 14 obtains the amount of light produced during the reaction process between the luminescent substrate and the labeling antibody bound to the antigen of the ample subjected to predetermined processing via a photomultiplier tube. The measuring unit 14 sends signals corresponding to the amount of light to the measurement controller 200 (refer to FIG. 1).

The disposal unit 17 is a unit for the disposal of cuvettes and waste fluid within the cuvettes after detection is completed, and the disposal unit has an aspiration part (not shown) for aspirating the waste fluid within the cuvette, and a disposal hole (not shown). After detection, the cuvette is moved from the measuring unit 14 to the disposal unit 17 by a catcher (not shown), the waste fluid within the cuvette is aspirated by the aspiration part and the cuvette from which the waste fluid has been aspirated is discarded through the disposal hole in the disposal unit 17.

The measurement controller 200 of the measuring section 2 has a CPU and a memory configured by a ROM, RAM or the like. The measurement controller 200 is configured to control each part of the measuring section 2 in accordance with signals output by the main body 400 of the control device 4 shown in FIG. 1. The controller 200 receives the signals sent from the measuring unit 14, converts the signals to measurement values, and analyzes the converted measurement values. The measurement controller 200 transmits the analysis results to the main body 400 of the control device 4.

As shown in FIG. 3, the reagent installation section 16 includes an annular table 162 on the inner side, and an annular table 163 on the outer side, when viewed from above.

The inner table 162 has a plurality of container holders capable of holding the R1 reagent container 100 which contains R1 reagent, and a plurality of container holders capable of holding R3 reagent container 120 which contains R3 reagent. These container holders accommodate a plurality of R1 reagent containers 100 on the inner side of the table 162 in an annular configuration, and the R1 reagent containers 100 are circumscribed on the outer side by the R3 reagent containers 120 which are arranged along the circumference, as shown in the drawing.

The outer table 163 has a plurality of container holders capable of holding the R2 reagent container which contains R2 reagent. These container holders accommodate R2 reagent containers 110 on the outside table 163 in an annular configuration so as to circumscribe the R1 reagent containers 100 on the outer side, as shown in the drawing.

The inner table 162 and the outer table 163 are configured to be horizontally rotatable in the circumferential direction via step motors which are not shown in the drawing. The reagent containers 100, 110, and 120 placed in the container holders are disposed at the reagent aspirating position to aspirate reagent through the reagent dispensers 6 through 8 by rotating the inner table 162 and the outer table 163.

Note that a cover which is not shown in the drawing is provided on the top surface of the reagent installation section 16 so as to cover both the reagent installation section 16 and the reactor 9, and an opening is formed in this cover to permit the insertion of the aspirating tubes 6 a through 8 a of the reagent dispensers 6 through 8.

As shown in FIG. 4, the reagent dispensers 6 through 8 have arms 6 b through 8 b, drive units 60 configured to move arms 6 b through 8 b vertically and rotate the alms 6 b through 8 b on shaft 6 c through 8 c, and aspirating tubes 6 a through 8 a attached at the tip of the arms 6 b through 8 b to aspirate and discharge the reagent in reagent containers 100, 110, and 120 which are held in container holder 16A of reagent installation section 16.

The drive unit 60 has a rotation motor 61, elevator motor 62, and a transmission unit 63 for transmitting the drive force of the rotation motor 61 and the elevator motor 62 to a shaft. The transmission unit 63 is configured by a rack and pinion mechanism and belt transmission unit for reducing the rotational force of, for example, the rotation motor 61, and converting the rotational force of the elevator motor 62 gear devices and belt transmission for transmitting force to the shafts 6 c through 8 c to a direct force in vertical directions and transmitting this force to the shafts 6 c through 8 c. Encoders 64 and 65 are provided to output signals according to the amount of rotational displacement of the rotation motor 61 and elevator motor 62, and the output signals of the encoders 64 and 65 are sent to the measurement controller 200. The measurement controller 200 detects the rotational position and vertical position of the aspirating tubes 6 a through 8 a by counting the output signals of the encoders 64 and 65. The encoders 64 and 65 therefore configure a position detection unit for detecting the position of the aspirating tubes 6 a through 8 a. Note that alternative configurations may be used as the position detection unit such as configurations which directly detect the position of the aspirating tubes 6 a through 8 a or configurations using an optical sensor or the like to detect a member which moves in association with the aspirating tubes 6 a through 8 a.

The measuring section 2 of the present embodiment also has, in addition to the various parts mentioned above, a liquid level detecting unit 20 (refer to FIG. 5) configured to detect the liquid level of reagent within the reagent containers 100, 110, and 120 installed in the reagent installation section 16. The structure of the liquid level detecting unit 20 will be described in detail later.

As shown in FIG. 1, the control device 4 is configured by a body part 400, and display/input part 410. The body part 400 has a CPU, a memory part such as a ROM, RAM, and hard disk, I/O interface, and image output interface.

The CPU of the body part 400 executes various programs installed in the memory part.

The I/O interface of the body part 400 receives the signals output from the display/input section 410. The image output interface of the body part 400 outputs image signals corresponding to the image data to the display/input part 410.

The display/input part 410 displays images based on the image signals received from the image output interface, and outputs instructions received from the user through the screen of the display/input part 410 to the I/O interface 406.

The communication interface of the body part 400 transmits signals from the body part 400 to the measurement controller 200 of the control section 2 on the body part 400 side, and receives signals sent from the measurement controller 200.

Reagent Aspiration Operation of the Reagent Dispensing Unit

As shown in FIG. 5, the liquid level detecting unit 20 has a position detector 65 which detects the vertical position of the aspirating tubes 6 a through 8 a, capacitance detector 21 which detects the change in capacitance between the aspirating tubes 6 a through 8 a and the surrounding environment, controller 22 which receives the output signals of the position detector 65 and capacitance detector 21, detects the liquid surface LS of the reagent L, and controls the drive unit 60 in accordance with the detected liquid level, and memory 23 which stores the background signal used to detect the reagent liquid level. The controller 22 and memory 23 are configured by the CPU and memory of the measurement controller 200.

The position detector 65 is configured by an encoder which outputs pulse signals corresponding to the rotation of the elevator motor 62 in the reagent dispensers 6 through 8, as previously described. The output of the position detector 65 is input to the controller 22.

Note that when a step motor is used as the elevator motor 62, a possible configuration will detect the position by the pulse count of a drive signal applied to the elevator motor 62 without providing the position detector 65.

The capacitance detector 21 is a capacitance sensor which detects changes in electrostatic capacity between the aspirating tubes 6 a through 8 a and the surrounding conductors, such changes being produced by the vertical movements of the aspirating tubes 6 a through 8 a. Specifically, the capacitance detector 21 incorporates an oscillation circuit 25 which oscillates a high frequency pulse, a peak-hold circuit 26 which obtains the peak value output of the oscillation circuit 25, and a differentiating circuit 27 which obtains the change in output of the peak-hold circuit 26, as shown in FIG. 6. Note that examples of the output signals s1, s2, and s3 of the circuits 25, 26, and 27 are shown in FIG. 6.

When the aspirating tubes 6 a through 8 a are lowered, the capacitance changes due to the change in distance between the aspirating tubes 6 a through 8 a and the reagent liquid level in the reagent containers 100, 110, and 120, and the capacitance changes greatly when the aspirating tube 6 a through 8 a contacts the liquid surface. The change in capacitance manifests as a change in amplitude of the output signal s1 which represents the output voltage of the oscillation circuit 25. Specifically, the amplitude of the output signal s1 of the oscillation circuit 25 increases when the capacitance is small, and the amplitude decreases when the capacitance increases.

The peak-hold circuit 26 obtains the peak value of the output signal s1 of the oscillation circuit 25 which corresponds to the magnitude of the capacitance C and output this peak value to the differentiating circuit 27. Although the output signal s2 of the peak-hold circuit 26 corresponds to the magnitude of the capacitance, the change itself is slight. Therefore, the rate of change in the output signal s2 of the peak-hold circuit 26 is obtained by the differentiating circuit 27. The output signal s3 of the differentiating circuit 27 therefore increases when the capacitance C changes rapidly due to the aspirating tube 6 a through 8 a contacting the liquid surface LS, and the contact between the liquid surface and the aspirating tube 6 a through 8 a can be detected in this way.

The output signal of the capacitance detector 21 is input to the controller 22. The controller 22 detects the position of the liquid surface LS of the reagent L from the output signal of the position detector 65 and the output signal of the capacitance detector 21. The controller 22 also controls the drive unit 60 to further lower the aspirating tubes 6 a through 8 a to a position at which the reagent L can be aspirated based on the detected position of the liquid surface LS of the reagent L

Although the reagent containers 100, 110 and 120 are installed in the reagent installation section 16, there are various conductive member such as metal panels and screws surrounding the reagent installation section 16 as well as the reagent installation section 16 itself. The output of the capacitance detector 21 is affected not only by the reagent L within the reagent containers 100, 110, and 120, but also by conductors surrounding the aspirating tubes 6 a through 8 a. Since the capacitance changes rapidly as the aspirating tubes 6 a through 8 a are moved in vertical directions and approach these conductors and move from these conductors, it becomes difficult to identify the change when the aspirating tube 6 a through 8 a makes contact with the liquid surface LS, and hence it becomes difficult to accurately detect the liquid surface LS. Since the capacitance changes rapidly when the aspirating tubes 6 a through 8 a move in vertical direction while accelerating or decelerating, it also becomes difficult to identify the change when the aspirating tubes 6 a through 8 a make contact with the liquid surface LS in this case.

The liquid level detecting unit 20 of the present embodiment is configured to accurately detect the liquid surface LS of the reagent L by considering the change in capacitance between the aspirating tubes 6 a through 8 a and the surrounding environment other than the reagent L within the reagent containers 100, 110, and 120, as described below.

Specifically, when reagent containers 100, 110, 120 are empty of reagent or reagent is consumed to the point the reagent cannot be aspirated by the aspirating tubes 6 a through 8 a, that is, the reagent containers 100, 110, 120 installed in reagent installation section 16 contain reagent below the dead volume level, the controller 22 of the liquid level detecting unit 20 moves the aspirating tubes 6 a through 8 a in a vertical direction and obtains the change in capacitance corresponding to the position of the aspirating tube 6 a through 8 a in a vertical direction. The controller 22 then stores this signal as the “background signal” (referred to as “reference signal” below) in the memory 23. In the present embodiment, the signal representing the capacitance when the aspirating tube 6 a through 8 a is moved is stored as the reference signal. The background signal is compared to the output signal of the capacitance detector 21 when the reagent is actually aspirated from the reagent containers 100, 110, 120 (referred to as “liquid level detection signal” or “real signal” below) to detect the liquid surface of the reagent L by eliminating the environmental influences around the reagent L.

Note that “when the aspirating tubes 6 a through 8 a are moving” refers to the interval from the starting point of the aspirating tube (for example, dead bottom point) to the arrival point (for example, dead top point). The operation of moving the aspirating tube is not specifically limited insofar as overall the operation moves from the starting point to the arrival point, and may be an operation of continuously moving from the starting point to the arrival point, or may be an operation of repeatedly moving with intermittent starts and stops.

Note that the background signal can be obtained and stored in memory 23 just once when the immunoanalyzer 1 is manufactured or installed, or can be obtained and stored in memory 23 automatically each time the power source of the immunoanalyzer 1 is turned on, that is, whenever the immunoanalyzer 1 is started. The output signal of the capacitance detector 21 changes when the metal parts are replaced and metal screws loosen around the containers. The background signal acquisition time and liquid level detection time are preferably closer than not in order to more accurately detect the liquid level. In the present embodiment, the background signal is automatically obtained at startup to cope with changes in the environment around the aspirating tubes 6 a through 8 a.

As shown in FIG. 7, conductors K such as metal panels and the like are present around the reagent containers 100, 110, 120. Reagent is not accommodated within the reagent containers 100, 110, 120. When the aspirating tube 6 a through 8 a is moved vertically in this situation, the obtained output signal of the capacitance detector 21 is on the right side of the graph. This output signal fluctuates greatly when the aspirating tube 6 a through 8 a approaches the conductor K and moves from the conductor K. This output signal also fluctuates greatly depending on the velocity change due to acceleration when the aspirating tube 6 a through 8 a starts to move downward from a higher stopped position.

As shown in FIG. 8, a reagent L is contained in the reagent container 100, 110, 120, and can be aspirated by the aspirating tube 6 a through 8 a. When the aspirating tube 6 a through 8 a is moved vertically in this situation, the obtained output signal of the capacitance detector 21 is in the center of the graph. This output signal fluctuates greatly when the aspirating tube 6 a through 8 a accelerates, when the aspirating tube 6 a through 8 a makes contact with the reagent L, and when the aspirating tube 6 a through 8 a approaches a nearby conductor K and moves from a nearby conductor K.

If the relationship between the background signal of FIG. 7 and the liquid level detection signal is considered, it becomes possible to grasp the change of the liquid level detection signal based only on the influences when contact is made with the reagent L. Specifically, just the signal when the reagent L is contacted may be obtained by acquiring the differential between the background signal and the liquid level detection signal. A graph representing the differential signals is shown at the right side in FIG. 8. In the graph, the change when the aspirating tube 6 a through 8 a approaches and moves from the nearby conductor K, and the change when the aspirating tubes 6 a through 8 a are accelerating are canceled, and the only remaining signal represents when the aspirating tube makes contact with the reagent L in the reagent container 100, 110, 120.

A bubble or membrane (the term “bubble” covers the concept of both hereinafter) LB produced during transport or the like may be simply present within the reagent container 100, 110, 120. The capacitance changes when the aspirating tube 6 a through 8 a makes contact with the bubble LB. In the graph showing the differential signals, it is understood that the differential signal changes when the not only when contact is made with the liquid surface LS of the reagent, but also when contact is made with the bubble LB.

The change in the differential signal which accompanies contact with the bubble LB is difficult to recognize as the change in the differential signal which accompanies contact with the liquid surface LS. In the present embodiment, measures are therefore taken to discriminate between when the aspirating tube 6 a through 8 a makes contact with the liquid surface LS and when the tube makes contact with the bubble LS. Specifically, the memory 23 of the liquid level detecting unit 20 stores an estimated position of the liquid surface LS of the reagent L beforehand. Then, when the differential signal changes between the background signal and the liquid level detection signal, whether or not the aspirating tube 6 a through 8 a has made contact with the liquid surface LS is determined by comparing the position of the aspirating tube 6 a through 8 a and the estimated position of the liquid level.

The specific control sequences of the acquisition of the background signal, and reagent liquid level detection mentioned above, are described in detail below with reference to FIGS. 9 through 11. Note that in FIGS. 9 through 11 the term “background signal” is abbreviated to “BG signal.”

[Background Signal Acquisition]

Empty reagent containers 100, 110, 120 or reagent containers 100, 110, 120 containing reagent below dead volume are pre-installed by a service person at predetermined positions on the inner table 162 and outer table 163 of the reagent installation section 16.

As shown in FIG. 9, the controller 22 controls the drive unit 60 to lower the aspirating tubes 6 a through 8 a when the power is switched on to the immunoanalyzer 1 (step S1).

The controller 22 obtains the position of the aspirating tubes 6 a through 8 a in the vertical direction from the position detector 65 (step S2), and obtains the output signal of the capacitance detector 21 as the background signal B1 (step S3).

The controller 22 associates the background signal B1 with the position of the aspirating tube 6 a through 8 a in the vertical direction, and stores the data in the memory 23 (step S4).

The controller 22 then determines whether the aspirating tube 6 a through 8 a has arrived at the dead bottom point (step S5). The dead bottom point is set at a position near but not touching the bottom of the reagent container 100, 110, 120 installed in the reagent installation section 16. The process returns to step S2 when the aspirating tube 6 a through 8 a has not arrived at the dead bottom point, and the process advances to step S6 when the aspirating tube 6 a through 8 a has reached the dead bottom point.

In step S6, the controller 22 raises the aspirating tubes 6 a through 8 a, and obtains a background signal B2 and the position of the aspirating tube 6 a through 8 a in the vertical direction (steps S7, S8). The controller 22 associates the background signal B2 with the position of the aspirating tube 6 a through 8 a in the vertical direction, and stores the data in the memory 23 (step S9). The controller 22 repeats steps S7 through S9 until the aspirating tubes 6 a through 8 a are at the dead top point, and the process of stopping the aspirating tubes 6 a through 8 a ends (step S11) when the controller 22 determines (that the aspirating tubes 6 a through 8 a have reached the top dead point (step S10).

When the aspirating tubes 6 a through 8 a are lowered background signals B1 and B2 are obtained by the operation described above when raising the tubes, and the data are stored in memory 23.

Note that the acquisition of background signals B1 and B2 as per above is accomplished for each reagent dispenser 6 through 8 containing reagents R1 through R3, respectively. Suitable background signals B1 and B2 therefore are obtained for each reagent dispenser 6 through 8.

When the background signals B1 and B2 obtained by the controller 22 differ in magnitude from the background signals stored in the memory 23 (for example, when the differential of the former and latter background signals exceeds a predetermined threshold value), an error is considered to have occurred due to some large environmental fluctuation around the aspirating tubes 6 a through 8 a, as well as dysfunction of a circuit or sensor in the system obtaining the background signals. Therefore, the controller 22 sends a summary to the control device 4, and an error message is shown on the display/input section 410, and an audio or optical warning is issued to alert the user by warning part.

[Reagent Aspiration Operation]

As shown in FIGS. 10 and 11, the controller 22 controls the drive units 60 to lower the aspirating tubes 6 a through 8 a (step S21). The positions of the aspirating tubes 6 a through 8 a in the vertical direction are obtained from the position detector 65 (step S22), and the output signal of the capacitance detector 21 is obtained as the liquid level detection signal A1 (step S23).

The controller 22 reads the background signals B1 corresponding to the positions of the aspirating tube 6 a through 8 a from the memory 23 (step S24), compares the background signal B1 to the liquid level detection signal A1 and determines the differential signal C1 (C1=A1−B1) (step S25). The differential signal C1 obtained at this time is equivalent to a signal represented in the graph on the right side of FIG. 8.

The controller 22 determines whether the differential signal C1 is greater than a predetermined threshold value D1 (refer to FIG. 8) (step S26), and the process returns to step S22 when the signal C1 is less than the threshold D1, and the process advances to step S27 when the signal C1 is greater than the threshold D1.

In step S27, the controller 22 determines whether the aspirating tubes 6 a through 8 a are at the estimated position of the liquid surface LS. The estimated position is obtained in step S37 and will be described later. When initially performing the process of step S27, since the estimated position does not yet exist, the position of the liquid surface corresponding to the capacity when, for example, a new reagent container 100, 110, 120 is installed in reagent installation section 16 is set as the estimated position, and stored in memory 23.

Although the estimated position of the liquid surface LS may be a value represented by a point in the vertical direction, a predetermined width (for example, about 1 mm) in the vertical direction is set as the value in the present embodiment. When the leading end of the aspirating tube 6 a through 8 a matches the liquid level estimated position, that is, when the value is within the predetermined width, the position is determined to be the liquid surface LS of the reagent L, and the process advances to step S28. When the leading end of the aspirating tube 6 a through 8 a does not match the liquid level estimated position, the process advances to step S30, then the process returns to step S22.

The controller 22 stops the lowering operation of the aspirating tubes 6 a through 8 a in step S28, and suctions the reagent L within the reagent containers 100, 110, 120 in step S29. The aspirating operation of the reagent L includes an operation of lowering the aspirating tubes 6 a through 8 a only a predetermined amount from the liquid level detection position of the reagent L. This predetermined amount is set at an amount which allows the aspirating tubes 6 a through 8 a to remain in the liquid even though the liquid surface LS declines in conjunction with the aspiration of the reagent L.

On the other hand, in step S30 the controller 22 sets the bubble contact flag to [1]. In step S26, when the differential signal C1 is determined to be greater than the predetermined threshold value D1, the aspirating tubes 6 a through 8 a are considered to have made contact with the liquid surface LS of the reagent L or contact with the bubble LB above the liquid surface LS. In step S27, when the leading end of the aspirating tube 6 a through 8 a does not match the estimated position of the liquid level, there is a very high possibility that the aspirating tube 6 a through 8 a has made contact with the bubble LB. Therefore, in this case the aspirating tube 6 a through 8 a is determined to have made contact with the bubble LB, and the bubble contact flag is raised. Note that the bubble contact flag is used when the aspirating tube 6 a through 8 a is washed after reagent aspiration in step S41 to be described later.

The controller 22 then raises the aspirating tubes 6 a through 8 a (step S31), obtains the vertical direction position of the aspirating tubes 6 a through 8 a from the position detector 65 (step S32), and obtains the output signal of the capacitance detector 21 as the liquid level detection signal A2 (step S33).

The controller 22 reads the background signals B2 corresponding to the positions of the aspirating tube 6 a through 8 a from the memory 23 (step S34), compares the background signal B2 to the liquid level detection signal A2 and determines the differential signal C2 (C1=A2−B2) (step S35). The differential signal C2 obtained at this time is equivalent to a signal represented in the graph on the right side of FIG. 8.

The controller 22 determines whether the differential signal C2 is greater than a predetermined threshold value D2 (step S36), and the process returns to step S32 when the signal C2 is less than the threshold D2, and the process advances to step S37 when the signal C2 is greater than the threshold D2.

When the differential signal C2 is greater than the threshold value D2, the controller 22 stores the positions of aspirating tubes 6 a through 8 a as the next estimated position of the liquid level being used in memory 23, in step S37.

Thereafter, the controller 22 obtains the position of the aspirating tubes 6 a through 8 a (step S38), determines whether the aspirating tube 6 a through 8 a has reached the top dead point (step S39), and stops the raising of the aspirating tube 6 a through 8 a when the tube has reached the top dead point (step S40).

Thereafter, the washing process of the aspirating tubes 6 a through 8 a is executed (step S41), and the process ends.

[Aspiration Tube Washing Unit Structure and Operating Sequence]

The aspirating tube washing process of step S41 in FIG. 11 is described in detail below.

The measuring section 2 of the present embodiment is structurally described above, however, an aspiration tube washing unit 220 is also provided to wash the aspirating tubes 6 a through 8 a after reagent is aspirated and discharged. The aspirating tube washing unit 220 has a wash container 221, and the wash container 221 has a washing orifice 222 through which the aspirating tubes 6 a through 8 a are inserted, and a washing nozzle 223 which discharges washing liquid into the wash container 221. The wash container 221 is arranged within the range of movement of the aspirating tubes 6 a through 8 a.

The washing orifice 222 is an opening on the top end of the wash container 221, and the aspirating tubes 6 a through 8 a can be inserted from this opening. The washing nozzle 223 is configured to wash the aspirating tubes 6 a through 8 a by discharging washing liquid obliquely from above through the washing orifice 222, and spraying the washing liquid on the aspirating tubes 6 a through 8 a inserted in the washing orifice 222. The washing range of the aspirating tubes 6 a through 8 a can be changed by changing the amount of insertion of the aspirating tubes 6 a through 8 a through the washing orifice 222.

The aspirating tube washing process of step S41 of FIG. 11 is described below referring to FIG. 12.

The controller 22 determines whether the bubble contact flag obtained in step 30 of FIG. 10 is set to [1] (step S51).

The process advances to step S52 when the bubble contact flag is set to [1], and the process continues to step S53 when the flag is not set to [1].

Since there is a high possibility that the aspirating tube 6 a through 8 a has made contact with the bubble LB when the bubble contact flag is set to [1] as previously described, the leading end of the aspirating tube 6 a through 8 a makes contact with the reagent L in a relatively broad range. Therefore, when the bubble contact flag is set to [1], a wider range of 70 mm from the bottom end of the aspirating tube 6 a through 8 a is washed in step S52. When the bubble contact flag is not set to [1], a narrower range of 10 mm from the bottom end of the aspirating tube 6 a through 8 a is washed in step S53. In this way the aspirating tubes 6 a through 8 a are reliably washed even when contact has been made with the bubble, and contamination is prevented.

In step S54, the controller 22 initializes the bubble contact flag to [0] and the process ends.

Note that the specific numerical values of the washing range of the aspirating tubes 6 a through 8 a are examples, and the present invention is not limited to these values. When the bubble contact flag is set to [1] as described previously, a signal may be sent to the control device 4 to display a message in the control device 4 indicating the aspirating tube 6 a through 8 a has made contact with the bubble.

Since the liquid level is detected by the liquid level detecting unit 20 when the reagent L is aspirated from the reagent container 100, 110, 120 in the present embodiment described above, the aspirating tubes 6 a through 8 a can be reliably inserted into the reagent L for aspiration, the aspirating tubes 6 a through 8 a can be minimally inserted into the reagent L, and contamination can be prevented.

Since the liquid level detecting unit 20 detects the liquid surface LS of the reagent L based on the liquid level detection signals (real signals) A1 and A2 and the background signals (reference signals B1 and B2) stored in memory 23, the liquid surface LS of the reagent L can be accurately detected by excluding the influence of conductors K present around the reagent containers 100, 110, 120, influence of changes in the moving speed of the aspirating tubes 6 a through 8 a, and the influence of loosening metal screws and replaced metal parts around the containers. Because the influence of changes in moving speed of the aspirating tubes 6 a through 8 a is eliminated, the aspirating tubes 6 a through 8 a can operate at higher speed and the measurement cycle time can be reduced.

The liquid level detecting unit 20 appropriately recognizes whether the aspirating tubes 6 a through 8 a have made contact with the liquid surface LS or made contact with the bubble LB by using the estimated position of the liquid surface LS of the reagent L. Erroneous aspiration of reagent L therefore is prevented when the bubble LB is mistakenly detected as the liquid surface LS.

The measuring section 2 of the present embodiment can reliably prevent contamination because the liquid level detecting unit 20 detects whether the aspirating tubes 6 a through 8 a make contact with the bubble LB, and wash a wide range of the aspirating tubes 6 a through 8 a when the aspirating tube has made contact with the bubble LB.

Note that the present invention is not limited to the above described embodiment and may be variously modified insofar as such modifications are within the scope of the claims.

For example, although empty reagent containers or reagent containers holding reagent below dead volume are installed in the container holders of the reagent installation section when obtaining the background signal, the reagent need not necessarily be installed inasmuch as the background signal also may be obtained when the reagent container is not installed. However, an actually accurate background signal can be obtained by installing the reagent containers.

Although the background signal is automatically obtained each time the power is switched on for the immunoanalyzer 1 in the above embodiment, the present invention is not limited to this configuration. For example, the background signal can be automatically obtained and stored in memory 23 when the reagent containers 100, 110, 120 are empty, or the liquid L within the reagent containers 100, 110, 120 is below dead volume. In this case, for example, the estimated position can be stored and whether the estimated position is less than the liquid level when the reagent in the container is at dead volume can be determined in step S37 of FIG. 11. When it is determined that the estimated position is less than the liquid level when the reagent in the container is at dead volume, this determination result preferably becomes a trigger to start the background signal acquisition process shown in FIG. 9.

Although the previously described liquid level detecting unit detects the liquid level of the reagent contained in a reagent container, the liquid level detecting unit also is applicable to detecting the liquid level of a sample held in a sample container.

Although the control device in the above embodiment is integrated with a measuring section, the control device also may be configured as a stand alone personal computer or the like.

Although the background signal in the device is obtained and stored in memory when the power is switched on to the immunoanalyzer, when the reagent container is empty, when the apparatus is manufactured, or at the time of installation in the above embodiment, the background signal also may be obtained by a separate immunoanalyzer, for example a prototype or master device.

Although the immunoanalyzer 1 is described by way of example of an analyzer of the present invention in the above embodiment, the present invention is not limited to this embodiment. For example, the present invention also is applicable to other clinical analyzers such as blood coagulation measuring apparatus, multi item blood cell analyzer, urine component analyzer, gene amplification measuring apparatus and the like.

Although the output signal of the capacitance detector is associated with the position in the vertical direction of the aspirating tubes 6 a through 8 a and stored as the reference signal representing a signal when the aspirating tube is moving in the above embodiment, the present invention is not limited to this embodiment. For example, the output signal also may be associated and stored when a predetermined time has elapsed since the start of movement of the aspirating tubes 6 a through 8 a, or the output signal may be associated and stored with the travel distance of the aspirating tubes 6 a through 8 a.

Although an electrostatic capacity sensor is used as the capacitance detector 21 in the above embodiment, the detector is not specifically limited insofar as the capacitance detector 21 can detect changes in the physical characteristics between the aspirating tube and the environment surrounding the aspirating tube including the liquid level of the liquid within a liquid container. For example, in addition to an electrostatic capacity sensor, a voltage sensor, ultrasonic sensor, electrical resistance sensor or the like may be used as the capacitance detector 21. 

What is claimed is:
 1. An analyzer comprising: a container holder configured to hold a container containing a liquid; an aspirating tube configured to aspirate the liquid from the container held by the container holder; a drive part configured to transfer the aspirating tube; a detector configured to output a signal based on a physical characteristic between the aspirating tube and a liquid surface in the container; and a memory configured to store, as a reference signal, the signal output from the detector when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder; and a controller configured to detect a liquid level position in the container, based on the reference signal and a real signal output by the detector when the aspirating tube is transferred for an aspiration operation of the liquid.
 2. The analyzer of claim 1, wherein the reference signal is output by the detector when the aspirating tube is being transferred in a vertical direction.
 3. The analyzer of claim 2, wherein the controller detects the liquid level position based on the reference signal and the real signal output by the detector when the aspirating tube is transferred downward to aspirate the liquid from the container.
 4. The analyzer of claim 3, wherein the controller detects the liquid level position based on a position of the aspirating tube when the real signal is obtained, if a differential between the real signal and the reference signal exceeds a predetermined threshold value.
 5. The analyzer of claim 4, wherein the memory stores an estimated position of the liquid level; and the controller detects a position of a leading end of the aspirating tube as the liquid level position if the differential between the real signal and the reference signal exceeds the predetermined threshold value and the leading end of the aspirating tube is at the estimated position when the real signal is obtained.
 6. The analyzer of claim 5, further comprising: a washing part configured to wash a range including the leading end of the aspirating tube; wherein the controller controls the washing part to wash a first range when the differential does not exceed the predetermined threshold value before the liquid level position is detected and controls the washing part to wash a second range larger than the first range when the differential exceeds the predetermined threshold value before the liquid level position is detected.
 7. The analyzer of claim 6, further comprising: a display part; wherein the controller shows bubble detection information on the display part when the differential exceeds the predetermined threshold value before the liquid level position is detected.
 8. The analyzer of claim 5, wherein the controller detects the liquid level position based on the reference signal and the real signal output by the detector when the aspirating tube is raised after the liquid has been aspirated from the container.
 9. The analyzer of claim 8, wherein the controller detects the liquid level position based on a position of the aspirating tube when the real signal is obtained, if a differential between the real signal and the reference signal exceeds a predetermined threshold value.
 10. The analyzer of claim 9, wherein the controller stores the detected liquid level position in the memory as the estimated position of the liquid level for a next aspiration operation.
 11. The analyzer of claim 1, wherein the reference signal is output by the detector in a state in which an empty container or a container containing liquid below a dead volume is held by the container holder.
 12. The analyzer of claim 1, wherein the reference signal is output by the detector each time a power source of the analyzer is switched on.
 13. The analyzer of claim 1, wherein the reference signal is output by the detector each time a reagent container becomes empty.
 14. The analyzer of claim 1, further comprising: a warning part; wherein the memory stores a reference signal each time the reference signal is output by the detector, the controller operates the warning part when a differential between a newly obtained reference signal and a previous reference signal stored in the memory exceeds a threshold value.
 15. The analyzer of claim 1, wherein a plurality of aspirating tubes are provided, and the memory stores respective reference signals for each aspirating tube.
 16. The analyzer of claim 1, wherein the liquid is a sample supplied to the analyzer, or a reagent used in analysis.
 17. The analyzer of claim 1, wherein the detector is configured to output a signal based on an electrostatic capacity between the aspirating tube and the liquid surface in the container.
 18. The analyzer of claim 1, wherein the liquid is a reagent the analyzer further comprises: a preparation portion configured to prepare a measurement sample from the reagent and a sample, and a measurement portion configured to measure components contained in the measurement sample.
 19. An analyzer comprising: a container holder configured to hold a container containing a liquid; an aspirating tube configured to aspirate the liquid from the container held by the container holder; a drive part configured to transfer the aspirating tube; a controller configured to control the drive part; a detector configured to output a signal based on a physical characteristic between the aspirating tube and a liquid surface in the container; and a memory configured to store the signal output by the detector; wherein the controller is configured to; store as a reference signal in the memory, the signal output by the detector when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder; and detect the liquid level position in the container, based on the reference signal and a real signal output by the detector when the aspirating tube is transferred for an aspiration operation of the liquid.
 20. A method of detecting a liquid level in an analyzer comprising: a step of transferring an aspirating tube to aspirate a liquid from a container held in a container holder; a step of outputting, as a real signal, a signal based on a physical characteristic between the aspirating tube and a liquid surface in the container, when the aspirating tube is being transferred for an aspiration operation of the liquid; and a step of detecting the liquid level position in the container based on the real signal and a reference signal that is based on a physical characteristic between the aspirating tube and the liquid surface in the container when the aspirating tube is being transferred under a condition that the container containing the liquid which can be aspirated by the aspirating tube is not being held by the container holder. 